#setwd('/afs/inf.ed.ac.uk/user/s17/s1725186/Documents/PhD-Models/FirstPUModel/RMarkdowns')
library(tidyverse) ; library(reshape2) ; library(glue) ; library(plotly) ; library(dendextend)
library(RColorBrewer) ; library(viridis) ; require(gridExtra) ; library(GGally)
library(knitr)
# Gandal dataset
load('./../Data/preprocessed_data.RData')
datExpr = datExpr %>% data.frame
DE_info = DE_info %>% data.frame
# GO Neuronal annotations: regex 'neuron' in GO functional annotations and label the genes that make a match as neuronal
GO_annotations = read.csv('./../Data/genes_GO_annotations.csv')
GO_neuronal = GO_annotations %>% filter(grepl('neuron', go_term)) %>%
mutate('ID'=as.character(ensembl_gene_id)) %>%
dplyr::select(-ensembl_gene_id) %>% distinct(ID) %>%
mutate('Neuronal'=1)
# SFARI Genes
SFARI_genes = read_csv('./../../../SFARI/Data/SFARI_genes_01-03-2020_w_ensembl_IDs.csv')
SFARI_genes = SFARI_genes[!duplicated(SFARI_genes$ID) & !is.na(SFARI_genes$ID),]
# Clusterings
clusterings = read_csv('./../Data/clusters.csv')
# Update DE_info with SFARI and Neuronal information
genes_info = DE_info %>% mutate('ID'=rownames(.)) %>% left_join(SFARI_genes, by='ID') %>%
mutate(`gene-score`=ifelse(is.na(`gene-score`), 'Others', `gene-score`)) %>%
left_join(GO_neuronal, by='ID') %>% left_join(clusterings, by='ID') %>%
mutate(Neuronal=ifelse(is.na(Neuronal), 0, Neuronal)) %>%
mutate(gene.score=ifelse(`gene-score`=='Others' & Neuronal==1, 'Neuronal', `gene-score`),
significant=padj<0.05 & !is.na(padj))
clustering_selected = 'DynamicHybrid'
genes_info$Module = genes_info[,clustering_selected]
dataset = read.csv(paste0('./../Data/dataset_', clustering_selected, '.csv'))
dataset$Module = dataset[,clustering_selected]
top_modules = dataset %>% arrange(desc(MTcor)) %>% filter(abs(MTcor)>0.9) %>% dplyr::pull(Module) %>%
unique %>% as.character
# Correct SFARI Scores
dataset$gene.score = genes_info$gene.score
# Load Enrichment Analyses
# GSEA
load('./../Data/GSEA_bonferroni.RData')
GSEA_GO = enrichment_GO
GSEA_DGN = enrichment_DGN
GSEA_DO = enrichment_DO
GSEA_KEGG = enrichment_KEGG
GSEA_Reactome = enrichment_Reactome
GSEA_SFARI = enrichment_SFARI
# ORA
load('./../Data/ORA_bonferroni.RData')
ORA_GO = enrichment_GO
ORA_DGN = enrichment_DGN
ORA_DO = enrichment_DO
ORA_KEGG = enrichment_KEGG
ORA_Reactome = enrichment_Reactome
ORA_SFARI = enrichment_SFARI
SFARI_colour_hue = function(r) {
pal = c('#FF7631','#FFB100','#E8E328','#8CC83F','#62CCA6','#59B9C9','#b3b3b3','#808080','gray','#d9d9d9')[r]
}
rm(DE_info, GO_annotations, clusterings, getinfo, mart, dds, GO_neuronal, enrichment_GO, enrichment_DO,
enrichment_DGN, erichment_DO, enrichment_KEGG, enrichment_Reactome)
# FUNCTIONS
compare_methods = function(GSEA_list, ORA_list){
for(top_module in top_modules){
cat(paste0(' \n \n \n \nEnrichments for Module ', top_module, ' (MTcor=',
round(dataset$MTcor[dataset$Module==top_module][1],2), '): \n \n'))
GSEA = GSEA_list[[top_module]]
ORA = ORA_list[[top_module]]
cat(paste0('GSEA has ', nrow(GSEA), ' enriched terms \n'))
cat(paste0('ORA has ', nrow(ORA), ' enriched terms \n'))
cat(paste0(sum(ORA$ID %in% GSEA$ID), ' terms are enriched in both methods \n'))
plot_data = GSEA %>% mutate(pval_GSEA = p.adjust) %>% dplyr::select(ID, Description, NES, pval_GSEA) %>%
inner_join(ORA %>% mutate(pval_ORA = p.adjust) %>%
dplyr::select(ID, pval_ORA, GeneRatio, qvalue), by = 'ID')
if(nrow(plot_data)>0) print(plot_data %>% mutate(pval_mean = pval_ORA + pval_GSEA) %>%
arrange(pval_mean) %>% dplyr::select(-pval_mean) %>% kable)
}
}
plot_results = function(GSEA_list, ORA_list){
l = htmltools::tagList()
for(i in 1:length(top_modules)){
GSEA = GSEA_list[[top_modules[i]]]
ORA = ORA_list[[top_modules[i]]]
plot_data = GSEA %>% mutate(pval_GSEA = p.adjust) %>% dplyr::select(ID, Description, NES, pval_GSEA) %>%
inner_join(ORA %>% mutate(pval_ORA = p.adjust) %>% dplyr::select(ID, pval_ORA), by = 'ID')
if(nrow(plot_data)>5){
min_val = min(min(plot_data$pval_GSEA), min(plot_data$pval_ORA))
max_val = max(max(max(plot_data$pval_GSEA), max(plot_data$pval_ORA)),0.05)
ggp = ggplotly(plot_data %>% ggplot(aes(pval_GSEA, pval_ORA, color = NES)) +
geom_point(aes(id = Description)) +
geom_vline(xintercept = 0.05, color = 'gray', linetype = 'dotted') +
geom_hline(yintercept = 0.05, color = 'gray', linetype = 'dotted') +
ggtitle(paste0('Enriched terms in common for Module ', top_modules[i])) +
scale_x_continuous(limits = c(min_val, max_val)) +
scale_y_continuous(limits = c(min_val, max_val)) +
xlab('Corrected p-value for GSEA') + ylab('Corrected p-value for ORA') +
scale_colour_viridis(direction = -1) + theme_minimal() + coord_fixed())
l[[i]] = ggp
}
}
return(l)
}
compare_methods(GSEA_KEGG, ORA_KEGG)
Enrichments for Module #73B000 (MTcor=0.94):
GSEA has 42 enriched terms
ORA has 4 enriched terms
4 terms are enriched in both methods
| ID | Description | NES | pval_GSEA | pval_ORA | GeneRatio | qvalue |
|---|---|---|---|---|---|---|
| hsa05034 | Alcoholism | 2.459042 | 0.0058904 | 0.0000000 | 54/649 | 0.0000000 |
| hsa05322 | Systemic lupus erythematosus | 3.153606 | 0.0059327 | 0.0000000 | 45/649 | 0.0000000 |
| hsa05202 | Transcriptional misregulation in cancer | 2.203888 | 0.0059057 | 0.0009106 | 36/649 | 0.0002912 |
| hsa05203 | Viral carcinogenesis | 1.947256 | 0.0058775 | 0.0556118 | 35/649 | 0.0133392 |
Enrichments for Module #EE8045 (MTcor=0.93):
GSEA has 46 enriched terms
ORA has 4 enriched terms
4 terms are enriched in both methods
| ID | Description | NES | pval_GSEA | pval_ORA | GeneRatio | qvalue |
|---|---|---|---|---|---|---|
| hsa05168 | Herpes simplex virus 1 infection | 2.552720 | 0.0043657 | 0.0000008 | 58/380 | 4.00e-07 |
| hsa05034 | Alcoholism | 2.468803 | 0.0049104 | 0.0000671 | 28/380 | 2.21e-05 |
| hsa05322 | Systemic lupus erythematosus | 3.116966 | 0.0051117 | 0.0000000 | 27/380 | 0.00e+00 |
| hsa05203 | Viral carcinogenesis | 2.006682 | 0.0048435 | 0.0030437 | 27/380 | 7.53e-04 |
Enrichments for Module #00B9E3 (MTcor=-0.93):
GSEA has 47 enriched terms
ORA has 4 enriched terms
3 terms are enriched in both methods
| ID | Description | NES | pval_GSEA | pval_ORA | GeneRatio | qvalue |
|---|---|---|---|---|---|---|
| hsa05033 | Nicotine addiction | 2.280163 | 0.0054286 | 0.0108575 | 13/699 | 0.0041822 |
| hsa04020 | Calcium signaling pathway | 1.969428 | 0.0044889 | 0.0143596 | 38/699 | 0.0041822 |
| hsa04728 | Dopaminergic synapse | 2.211123 | 0.0047074 | 0.0828857 | 27/699 | 0.0181054 |
Enrichments for Module #84AD00 (MTcor=-0.93):
GSEA has 37 enriched terms
ORA has 0 enriched terms
0 terms are enriched in both methods
compare_methods(GSEA_Reactome, ORA_Reactome)
Enrichments for Module #73B000 (MTcor=0.94):
GSEA has 170 enriched terms
ORA has 78 enriched terms
76 terms are enriched in both methods
| ID | Description | NES | pval_GSEA | pval_ORA | GeneRatio | qvalue |
|---|---|---|---|---|---|---|
| R-HSA-3247509 | Chromatin modifying enzymes | 2.278873 | 0.0243207 | 0.0000002 | 57/814 | 0.0000000 |
| R-HSA-4839726 | Chromatin organization | 2.278873 | 0.0243207 | 0.0000002 | 57/814 | 0.0000000 |
| R-HSA-9006931 | Signaling by Nuclear Receptors | 2.381399 | 0.0243898 | 0.0000002 | 55/814 | 0.0000000 |
| R-HSA-8878171 | Transcriptional regulation by RUNX1 | 2.201971 | 0.0244490 | 0.0000006 | 50/814 | 0.0000000 |
| R-HSA-157118 | Signaling by NOTCH | 2.214671 | 0.0244334 | 0.0000404 | 47/814 | 0.0000006 |
| R-HSA-8939211 | ESR-mediated signaling | 2.590280 | 0.0244928 | 0.0000000 | 53/814 | 0.0000000 |
| R-HSA-201681 | TCF dependent signaling in response to WNT | 2.034284 | 0.0244125 | 0.0000857 | 45/814 | 0.0000013 |
| R-HSA-2559583 | Cellular Senescence | 2.480288 | 0.0246088 | 0.0000000 | 58/814 | 0.0000000 |
| R-HSA-9018519 | Estrogen-dependent gene expression | 2.977948 | 0.0247648 | 0.0000000 | 45/814 | 0.0000000 |
| R-HSA-212165 | Epigenetic regulation of gene expression | 2.462506 | 0.0247974 | 0.0000000 | 42/814 | 0.0000000 |
| R-HSA-211000 | Gene Silencing by RNA | 2.604248 | 0.0247987 | 0.0000000 | 43/814 | 0.0000000 |
| R-HSA-3214847 | HATs acetylate histones | 2.598060 | 0.0248199 | 0.0000000 | 46/814 | 0.0000000 |
| R-HSA-68875 | Mitotic Prophase | 2.803678 | 0.0248199 | 0.0000000 | 45/814 | 0.0000000 |
| R-HSA-2559580 | Oxidative Stress Induced Senescence | 2.699026 | 0.0249135 | 0.0000000 | 44/814 | 0.0000000 |
| R-HSA-1474165 | Reproduction | 3.018783 | 0.0249159 | 0.0000000 | 48/814 | 0.0000000 |
| R-HSA-8939236 | RUNX1 regulates transcription of genes involved in differentiation of HSCs | 2.515455 | 0.0249302 | 0.0000000 | 40/814 | 0.0000000 |
| R-HSA-977225 | Amyloid fiber formation | 3.054978 | 0.0249353 | 0.0000000 | 40/814 | 0.0000000 |
| R-HSA-1500620 | Meiosis | 3.047447 | 0.0249511 | 0.0000000 | 45/814 | 0.0000000 |
| R-HSA-73864 | RNA Polymerase I Transcription | 2.759782 | 0.0249660 | 0.0000000 | 40/814 | 0.0000000 |
| R-HSA-5617472 | Activation of anterior HOX genes in hindbrain development during early embryogenesis | 3.005654 | 0.0249660 | 0.0000000 | 40/814 | 0.0000000 |
| R-HSA-5619507 | Activation of HOX genes during differentiation | 3.005654 | 0.0249660 | 0.0000000 | 40/814 | 0.0000000 |
| R-HSA-5578749 | Transcriptional regulation by small RNAs | 2.925635 | 0.0250196 | 0.0000000 | 41/814 | 0.0000000 |
| R-HSA-5250913 | Positive epigenetic regulation of rRNA expression | 2.789580 | 0.0250196 | 0.0000000 | 40/814 | 0.0000000 |
| R-HSA-427413 | NoRC negatively regulates rRNA expression | 2.815700 | 0.0250196 | 0.0000000 | 39/814 | 0.0000000 |
| R-HSA-3214815 | HDACs deacetylate histones | 3.027939 | 0.0250215 | 0.0000000 | 42/814 | 0.0000000 |
| R-HSA-73854 | RNA Polymerase I Promoter Clearance | 2.732154 | 0.0250247 | 0.0000000 | 40/814 | 0.0000000 |
| R-HSA-2559582 | Senescence-Associated Secretory Phenotype (SASP) | 3.033487 | 0.0250294 | 0.0000000 | 44/814 | 0.0000000 |
| R-HSA-1912422 | Pre-NOTCH Expression and Processing | 3.120790 | 0.0250294 | 0.0000000 | 43/814 | 0.0000000 |
| R-HSA-5250941 | Negative epigenetic regulation of rRNA expression | 2.768677 | 0.0250294 | 0.0000000 | 40/814 | 0.0000000 |
| R-HSA-912446 | Meiotic recombination | 3.195567 | 0.0250397 | 0.0000000 | 40/814 | 0.0000000 |
| R-HSA-73772 | RNA Polymerase I Promoter Escape | 2.995694 | 0.0250505 | 0.0000000 | 39/814 | 0.0000000 |
| R-HSA-5250924 | B-WICH complex positively regulates rRNA expression | 2.968917 | 0.0250505 | 0.0000000 | 39/814 | 0.0000000 |
| R-HSA-5625740 | RHO GTPases activate PKNs | 3.100816 | 0.0250673 | 0.0000000 | 41/814 | 0.0000000 |
| R-HSA-1912408 | Pre-NOTCH Transcription and Translation | 3.192122 | 0.0250673 | 0.0000000 | 39/814 | 0.0000000 |
| R-HSA-8936459 | RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function | 3.120711 | 0.0250673 | 0.0000000 | 38/814 | 0.0000000 |
| R-HSA-2299718 | Condensation of Prophase Chromosomes | 3.346491 | 0.0250763 | 0.0000000 | 38/814 | 0.0000000 |
| R-HSA-5693571 | Nonhomologous End-Joining (NHEJ) | 2.460174 | 0.0250763 | 0.0000079 | 23/814 | 0.0000001 |
| R-HSA-212300 | PRC2 methylates histones and DNA | 3.227406 | 0.0250861 | 0.0000000 | 39/814 | 0.0000000 |
| R-HSA-606279 | Deposition of new CENPA-containing nucleosomes at the centromere | 2.897203 | 0.0250861 | 0.0000020 | 24/814 | 0.0000000 |
| R-HSA-774815 | Nucleosome assembly | 2.897203 | 0.0250861 | 0.0000020 | 24/814 | 0.0000000 |
| R-HSA-201722 | Formation of the beta-catenin:TCF transactivating complex | 3.071049 | 0.0250927 | 0.0000000 | 38/814 | 0.0000000 |
| R-HSA-73884 | Base Excision Repair | 2.546982 | 0.0250805 | 0.0000145 | 26/814 | 0.0000002 |
| R-HSA-3214841 | PKMTs methylate histone lysines | 2.710487 | 0.0251059 | 0.0000000 | 29/814 | 0.0000000 |
| R-HSA-5334118 | DNA methylation | 3.354489 | 0.0251134 | 0.0000000 | 37/814 | 0.0000000 |
| R-HSA-73728 | RNA Polymerase I Promoter Opening | 3.315263 | 0.0251134 | 0.0000000 | 37/814 | 0.0000000 |
| R-HSA-5625886 | Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 | 3.404989 | 0.0251148 | 0.0000000 | 37/814 | 0.0000000 |
| R-HSA-1221632 | Meiotic synapsis | 2.972464 | 0.0251148 | 0.0000000 | 27/814 | 0.0000000 |
| R-HSA-427389 | ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression | 3.166086 | 0.0251176 | 0.0000000 | 38/814 | 0.0000000 |
| R-HSA-2559586 | DNA Damage/Telomere Stress Induced Senescence | 2.789390 | 0.0251223 | 0.0000000 | 28/814 | 0.0000000 |
| R-HSA-73929 | Base-Excision Repair, AP Site Formation | 2.892719 | 0.0251228 | 0.0000000 | 24/814 | 0.0000000 |
| R-HSA-427359 | SIRT1 negatively regulates rRNA expression | 3.250592 | 0.0251285 | 0.0000000 | 38/814 | 0.0000000 |
| R-HSA-3214858 | RMTs methylate histone arginines | 2.859401 | 0.0251318 | 0.0000000 | 39/814 | 0.0000000 |
| R-HSA-157579 | Telomere Maintenance | 2.672800 | 0.0251318 | 0.0000037 | 25/814 | 0.0000001 |
| R-HSA-110328 | Recognition and association of DNA glycosylase with site containing an affected pyrimidine | 2.921933 | 0.0251435 | 0.0000000 | 24/814 | 0.0000000 |
| R-HSA-110329 | Cleavage of the damaged pyrimidine | 2.921933 | 0.0251435 | 0.0000000 | 24/814 | 0.0000000 |
| R-HSA-73928 | Depyrimidination | 2.921933 | 0.0251435 | 0.0000000 | 24/814 | 0.0000000 |
| R-HSA-3214842 | HDMs demethylate histones | 2.973280 | 0.0251648 | 0.0000000 | 31/814 | 0.0000000 |
| R-HSA-110330 | Recognition and association of DNA glycosylase with site containing an affected purine | 3.020401 | 0.0251918 | 0.0000000 | 24/814 | 0.0000000 |
| R-HSA-110331 | Cleavage of the damaged purine | 3.020401 | 0.0251918 | 0.0000000 | 24/814 | 0.0000000 |
| R-HSA-73927 | Depurination | 3.020401 | 0.0251918 | 0.0000000 | 24/814 | 0.0000000 |
| R-HSA-5693565 | Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks | 2.396526 | 0.0251252 | 0.0000692 | 23/814 | 0.0000010 |
| R-HSA-73886 | Chromosome Maintenance | 2.483760 | 0.0249846 | 0.0002307 | 27/814 | 0.0000033 |
| R-HSA-5693606 | DNA Double Strand Break Response | 2.396061 | 0.0251318 | 0.0000919 | 23/814 | 0.0000013 |
| R-HSA-171306 | Packaging Of Telomere Ends | 3.053194 | 0.0252883 | 0.0000000 | 23/814 | 0.0000000 |
| R-HSA-195258 | RHO GTPase Effectors | 1.840488 | 0.0241978 | 0.0012650 | 54/814 | 0.0000171 |
| R-HSA-1266695 | Interleukin-7 signaling | 2.306149 | 0.0253327 | 0.0004422 | 14/814 | 0.0000062 |
| R-HSA-69473 | G2/M DNA damage checkpoint | 2.341737 | 0.0249683 | 0.0014260 | 24/814 | 0.0000191 |
| R-HSA-5693607 | Processing of DNA double-strand break ends | 2.341501 | 0.0249725 | 0.0026772 | 24/814 | 0.0000353 |
| R-HSA-5693567 | HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA) | 2.235138 | 0.0248641 | 0.0223680 | 27/814 | 0.0002827 |
| R-HSA-2262752 | Cellular responses to stress | 1.632674 | 0.0477761 | 0.0000079 | 73/814 | 0.0000001 |
| R-HSA-195721 | Signaling by WNT | 1.690092 | 0.0484043 | 0.0001708 | 57/814 | 0.0000025 |
| R-HSA-6785807 | Interleukin-4 and Interleukin-13 signaling | 2.497601 | 0.0250439 | 0.0345609 | 21/814 | 0.0004310 |
| R-HSA-3108232 | SUMO E3 ligases SUMOylate target proteins | 2.093088 | 0.0245655 | 0.0462864 | 33/814 | 0.0005697 |
| R-HSA-194315 | Signaling by Rho GTPases | 1.594680 | 0.0715557 | 0.0064006 | 67/814 | 0.0000820 |
| R-HSA-5693538 | Homology Directed Repair | 2.171556 | 0.0248447 | 0.0534816 | 27/814 | 0.0006497 |
| R-HSA-2990846 | SUMOylation | 2.007948 | 0.0245606 | 0.0925865 | 33/814 | 0.0011103 |
Enrichments for Module #EE8045 (MTcor=0.93):
GSEA has 204 enriched terms
ORA has 76 enriched terms
73 terms are enriched in both methods
| ID | Description | NES | pval_GSEA | pval_ORA | GeneRatio | qvalue |
|---|---|---|---|---|---|---|
| R-HSA-3247509 | Chromatin modifying enzymes | 2.382042 | 0.0195119 | 0.0000001 | 43/495 | 0.0000000 |
| R-HSA-4839726 | Chromatin organization | 2.382042 | 0.0195119 | 0.0000001 | 43/495 | 0.0000000 |
| R-HSA-9006931 | Signaling by Nuclear Receptors | 2.206897 | 0.0196781 | 0.0001857 | 35/495 | 0.0000025 |
| R-HSA-8878171 | Transcriptional regulation by RUNX1 | 2.261105 | 0.0198763 | 0.0000101 | 35/495 | 0.0000001 |
| R-HSA-8939211 | ESR-mediated signaling | 2.449368 | 0.0200212 | 0.0000071 | 34/495 | 0.0000001 |
| R-HSA-2559583 | Cellular Senescence | 2.295883 | 0.0202788 | 0.0000003 | 34/495 | 0.0000000 |
| R-HSA-3108232 | SUMO E3 ligases SUMOylate target proteins | 2.071740 | 0.0203379 | 0.0000953 | 29/495 | 0.0000013 |
| R-HSA-2990846 | SUMOylation | 1.979695 | 0.0202852 | 0.0002019 | 29/495 | 0.0000027 |
| R-HSA-157118 | Signaling by NOTCH | 1.951114 | 0.0198181 | 0.0006943 | 32/495 | 0.0000091 |
| R-HSA-5693532 | DNA Double-Strand Break Repair | 2.018206 | 0.0205764 | 0.0001818 | 27/495 | 0.0000025 |
| R-HSA-212165 | Epigenetic regulation of gene expression | 2.555835 | 0.0208463 | 0.0000005 | 29/495 | 0.0000000 |
| R-HSA-9018519 | Estrogen-dependent gene expression | 2.861305 | 0.0208499 | 0.0000000 | 32/495 | 0.0000000 |
| R-HSA-3214847 | HATs acetylate histones | 2.695651 | 0.0209365 | 0.0000002 | 29/495 | 0.0000000 |
| R-HSA-68875 | Mitotic Prophase | 2.687889 | 0.0209365 | 0.0000008 | 28/495 | 0.0000000 |
| R-HSA-211000 | Gene Silencing by RNA | 2.636333 | 0.0209926 | 0.0000003 | 28/495 | 0.0000000 |
| R-HSA-5693567 | HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA) | 2.229659 | 0.0210738 | 0.0000847 | 24/495 | 0.0000012 |
| R-HSA-1474165 | Reproduction | 2.990888 | 0.0211577 | 0.0000017 | 26/495 | 0.0000000 |
| R-HSA-8939236 | RUNX1 regulates transcription of genes involved in differentiation of HSCs | 2.458849 | 0.0211600 | 0.0000014 | 26/495 | 0.0000000 |
| R-HSA-5693538 | Homology Directed Repair | 2.149519 | 0.0210048 | 0.0002120 | 24/495 | 0.0000028 |
| R-HSA-2559580 | Oxidative Stress Induced Senescence | 2.542884 | 0.0212351 | 0.0000000 | 29/495 | 0.0000000 |
| R-HSA-73864 | RNA Polymerase I Transcription | 2.772099 | 0.0214081 | 0.0000001 | 26/495 | 0.0000000 |
| R-HSA-5617472 | Activation of anterior HOX genes in hindbrain development during early embryogenesis | 2.867060 | 0.0214081 | 0.0000001 | 26/495 | 0.0000000 |
| R-HSA-5619507 | Activation of HOX genes during differentiation | 2.867060 | 0.0214081 | 0.0000001 | 26/495 | 0.0000000 |
| R-HSA-73854 | RNA Polymerase I Promoter Clearance | 2.753275 | 0.0214122 | 0.0000000 | 26/495 | 0.0000000 |
| R-HSA-1500620 | Meiosis | 3.041621 | 0.0214335 | 0.0000001 | 26/495 | 0.0000000 |
| R-HSA-2559582 | Senescence-Associated Secretory Phenotype (SASP) | 2.919696 | 0.0214362 | 0.0000000 | 29/495 | 0.0000000 |
| R-HSA-1912422 | Pre-NOTCH Expression and Processing | 2.995518 | 0.0214362 | 0.0000000 | 26/495 | 0.0000000 |
| R-HSA-5250941 | Negative epigenetic regulation of rRNA expression | 2.813435 | 0.0214362 | 0.0000002 | 25/495 | 0.0000000 |
| R-HSA-5250913 | Positive epigenetic regulation of rRNA expression | 2.745753 | 0.0214971 | 0.0000000 | 26/495 | 0.0000000 |
| R-HSA-427413 | NoRC negatively regulates rRNA expression | 2.872722 | 0.0214971 | 0.0000001 | 25/495 | 0.0000000 |
| R-HSA-5578749 | Transcriptional regulation by small RNAs | 2.865456 | 0.0214971 | 0.0000001 | 25/495 | 0.0000000 |
| R-HSA-73886 | Chromosome Maintenance | 2.490931 | 0.0215019 | 0.0000001 | 25/495 | 0.0000000 |
| R-HSA-5693607 | Processing of DNA double-strand break ends | 2.388162 | 0.0216587 | 0.0000002 | 24/495 | 0.0000000 |
| R-HSA-977225 | Amyloid fiber formation | 2.976874 | 0.0216948 | 0.0000001 | 24/495 | 0.0000000 |
| R-HSA-69473 | G2/M DNA damage checkpoint | 2.394096 | 0.0217515 | 0.0000005 | 23/495 | 0.0000000 |
| R-HSA-3214815 | HDACs deacetylate histones | 3.183673 | 0.0217741 | 0.0000000 | 26/495 | 0.0000000 |
| R-HSA-1912408 | Pre-NOTCH Transcription and Translation | 3.167742 | 0.0218376 | 0.0000000 | 26/495 | 0.0000000 |
| R-HSA-8936459 | RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function | 3.142486 | 0.0218376 | 0.0000000 | 26/495 | 0.0000000 |
| R-HSA-5625740 | RHO GTPases activate PKNs | 3.092663 | 0.0218376 | 0.0000000 | 24/495 | 0.0000000 |
| R-HSA-5250924 | B-WICH complex positively regulates rRNA expression | 2.945840 | 0.0218633 | 0.0000000 | 25/495 | 0.0000000 |
| R-HSA-73772 | RNA Polymerase I Promoter Escape | 3.024781 | 0.0218633 | 0.0000000 | 24/495 | 0.0000000 |
| R-HSA-201722 | Formation of the beta-catenin:TCF transactivating complex | 2.931072 | 0.0218740 | 0.0000000 | 26/495 | 0.0000000 |
| R-HSA-73884 | Base Excision Repair | 2.481520 | 0.0218801 | 0.0000001 | 23/495 | 0.0000000 |
| R-HSA-912446 | Meiotic recombination | 3.177327 | 0.0220402 | 0.0000000 | 24/495 | 0.0000000 |
| R-HSA-2559586 | DNA Damage/Telomere Stress Induced Senescence | 2.845834 | 0.0220842 | 0.0000000 | 23/495 | 0.0000000 |
| R-HSA-5693606 | DNA Double Strand Break Response | 2.658132 | 0.0220896 | 0.0000000 | 23/495 | 0.0000000 |
| R-HSA-157579 | Telomere Maintenance | 2.678335 | 0.0220896 | 0.0000000 | 23/495 | 0.0000000 |
| R-HSA-5693565 | Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks | 2.669142 | 0.0220969 | 0.0000000 | 23/495 | 0.0000000 |
| R-HSA-427389 | ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression | 3.166898 | 0.0221338 | 0.0000000 | 25/495 | 0.0000000 |
| R-HSA-3214858 | RMTs methylate histone arginines | 2.745707 | 0.0220896 | 0.0000751 | 18/495 | 0.0000011 |
| R-HSA-1221632 | Meiotic synapsis | 3.021587 | 0.0221711 | 0.0000000 | 25/495 | 0.0000000 |
| R-HSA-3214841 | PKMTs methylate histone lysines | 2.560910 | 0.0221843 | 0.0000000 | 21/495 | 0.0000000 |
| R-HSA-606279 | Deposition of new CENPA-containing nucleosomes at the centromere | 2.832629 | 0.0221954 | 0.0000000 | 25/495 | 0.0000000 |
| R-HSA-774815 | Nucleosome assembly | 2.832629 | 0.0221954 | 0.0000000 | 25/495 | 0.0000000 |
| R-HSA-212300 | PRC2 methylates histones and DNA | 3.195257 | 0.0221954 | 0.0000000 | 24/495 | 0.0000000 |
| R-HSA-2299718 | Condensation of Prophase Chromosomes | 3.267881 | 0.0222082 | 0.0000000 | 24/495 | 0.0000000 |
| R-HSA-5693571 | Nonhomologous End-Joining (NHEJ) | 2.633793 | 0.0222082 | 0.0000000 | 24/495 | 0.0000000 |
| R-HSA-427359 | SIRT1 negatively regulates rRNA expression | 3.259000 | 0.0223359 | 0.0000000 | 23/495 | 0.0000000 |
| R-HSA-5625886 | Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 | 3.428710 | 0.0224452 | 0.0000000 | 24/495 | 0.0000000 |
| R-HSA-5334118 | DNA methylation | 3.406522 | 0.0225278 | 0.0000000 | 23/495 | 0.0000000 |
| R-HSA-73728 | RNA Polymerase I Promoter Opening | 3.355613 | 0.0225278 | 0.0000000 | 23/495 | 0.0000000 |
| R-HSA-73929 | Base-Excision Repair, AP Site Formation | 2.824304 | 0.0225502 | 0.0000000 | 23/495 | 0.0000000 |
| R-HSA-110328 | Recognition and association of DNA glycosylase with site containing an affected pyrimidine | 2.857918 | 0.0225696 | 0.0000000 | 23/495 | 0.0000000 |
| R-HSA-110329 | Cleavage of the damaged pyrimidine | 2.857918 | 0.0225696 | 0.0000000 | 23/495 | 0.0000000 |
| R-HSA-73928 | Depyrimidination | 2.857918 | 0.0225696 | 0.0000000 | 23/495 | 0.0000000 |
| R-HSA-3214842 | HDMs demethylate histones | 2.792860 | 0.0227196 | 0.0000056 | 16/495 | 0.0000001 |
| R-HSA-110330 | Recognition and association of DNA glycosylase with site containing an affected purine | 2.955917 | 0.0227469 | 0.0000000 | 23/495 | 0.0000000 |
| R-HSA-110331 | Cleavage of the damaged purine | 2.955917 | 0.0227469 | 0.0000000 | 23/495 | 0.0000000 |
| R-HSA-73927 | Depurination | 2.955917 | 0.0227469 | 0.0000000 | 23/495 | 0.0000000 |
| R-HSA-171306 | Packaging Of Telomere Ends | 3.029616 | 0.0228412 | 0.0000000 | 23/495 | 0.0000000 |
| R-HSA-195258 | RHO GTPase Effectors | 1.829443 | 0.0191205 | 0.0124005 | 36/495 | 0.0001556 |
| R-HSA-201681 | TCF dependent signaling in response to WNT | 1.685616 | 0.0398614 | 0.0025650 | 30/495 | 0.0000331 |
| R-HSA-4551638 | SUMOylation of chromatin organization proteins | 2.046488 | 0.0442675 | 0.0000045 | 19/495 | 0.0000001 |
Enrichments for Module #00B9E3 (MTcor=-0.93):
GSEA has 90 enriched terms
ORA has 13 enriched terms
8 terms are enriched in both methods
| ID | Description | NES | pval_GSEA | pval_ORA | GeneRatio | qvalue |
|---|---|---|---|---|---|---|
| R-HSA-112316 | Neuronal System | 2.643595 | 0.0169280 | 0.0000000 | 92/1003 | 0.0000000 |
| R-HSA-112315 | Transmission across Chemical Synapses | 2.572379 | 0.0179982 | 0.0001390 | 56/1003 | 0.0000413 |
| R-HSA-112314 | Neurotransmitter receptors and postsynaptic signal transmission | 2.501833 | 0.0187214 | 0.0000146 | 48/1003 | 0.0000065 |
| R-HSA-1296071 | Potassium Channels | 2.209534 | 0.0204446 | 0.0020191 | 27/1003 | 0.0004499 |
| R-HSA-442755 | Activation of NMDA receptors and postsynaptic events | 2.413330 | 0.0206268 | 0.0036733 | 25/1003 | 0.0006548 |
| R-HSA-1296072 | Voltage gated Potassium channels | 2.533345 | 0.0222219 | 0.0164424 | 15/1003 | 0.0024423 |
| R-HSA-438064 | Post NMDA receptor activation events | 2.314038 | 0.0210213 | 0.0395355 | 21/1003 | 0.0050336 |
| R-HSA-438066 | Unblocking of NMDA receptors, glutamate binding and activation | 2.398864 | 0.0233726 | 0.0665704 | 10/1003 | 0.0059330 |
Enrichments for Module #84AD00 (MTcor=-0.93):
GSEA has 81 enriched terms
ORA has 0 enriched terms
0 terms are enriched in both methods
Plots of the results when there are more than 5 terms in common between methods:
plot_results(GSEA_Reactome, ORA_Reactome)
compare_methods(GSEA_GO, ORA_GO)
Enrichments for Module #73B000 (MTcor=0.94):
GSEA has 0 enriched terms
ORA has 60 enriched terms
0 terms are enriched in both methods
Enrichments for Module #EE8045 (MTcor=0.93):
GSEA has 0 enriched terms
ORA has 43 enriched terms
0 terms are enriched in both methods
Enrichments for Module #00B9E3 (MTcor=-0.93):
GSEA has 61 enriched terms
ORA has 95 enriched terms
31 terms are enriched in both methods
| ID | Description | NES | pval_GSEA | pval_ORA | GeneRatio | qvalue |
|---|---|---|---|---|---|---|
| GO:0044297 | cell body | 2.079677 | 0.0911222 | 0.0001105 | 92/1556 | 0.0000051 |
| GO:0034762 | regulation of transmembrane transport | 2.116789 | 0.0916164 | 0.0001355 | 91/1486 | 0.0000256 |
| GO:0043025 | neuronal cell body | 2.184071 | 0.0929181 | 0.0000414 | 84/1556 | 0.0000024 |
| GO:0098793 | presynapse | 2.655547 | 0.0931848 | 0.0000000 | 96/1556 | 0.0000000 |
| GO:0008324 | cation transmembrane transporter activity | 2.158107 | 0.0932786 | 0.0000008 | 86/1474 | 0.0000001 |
| GO:0015672 | monovalent inorganic cation transport | 2.246078 | 0.0934727 | 0.0000011 | 87/1486 | 0.0000005 |
| GO:0034765 | regulation of ion transmembrane transport | 2.244908 | 0.0934692 | 0.0000152 | 84/1486 | 0.0000048 |
| GO:0022890 | inorganic cation transmembrane transporter activity | 2.206956 | 0.0944116 | 0.0000004 | 82/1474 | 0.0000000 |
| GO:0097060 | synaptic membrane | 2.405299 | 0.0946283 | 0.0000000 | 99/1556 | 0.0000000 |
| GO:0098978 | glutamatergic synapse | 2.459707 | 0.0959919 | 0.0000186 | 72/1556 | 0.0000013 |
| GO:0033267 | axon part | 2.619227 | 0.0960165 | 0.0000371 | 71/1556 | 0.0000023 |
| GO:0022803 | passive transmembrane transporter activity | 2.060957 | 0.0971431 | 0.0000000 | 74/1474 | 0.0000000 |
| GO:0015267 | channel activity | 2.052951 | 0.0972098 | 0.0000001 | 73/1474 | 0.0000000 |
| GO:0046873 | metal ion transmembrane transporter activity | 2.109624 | 0.0980997 | 0.0000215 | 64/1474 | 0.0000015 |
| GO:0022838 | substrate-specific channel activity | 2.118246 | 0.0983712 | 0.0000000 | 70/1474 | 0.0000000 |
| GO:0098984 | neuron to neuron synapse | 2.317062 | 0.0973726 | 0.0010876 | 62/1556 | 0.0000331 |
| GO:0099572 | postsynaptic specialization | 2.289442 | 0.0973726 | 0.0010876 | 62/1556 | 0.0000331 |
| GO:0045211 | postsynaptic membrane | 2.326902 | 0.0986545 | 0.0000000 | 73/1556 | 0.0000000 |
| GO:0005216 | ion channel activity | 2.151565 | 0.0987311 | 0.0000000 | 70/1474 | 0.0000000 |
| GO:0042391 | regulation of membrane potential | 2.086443 | 0.0962160 | 0.0026710 | 67/1486 | 0.0002102 |
| GO:0005874 | microtubule | 2.056455 | 0.0960165 | 0.0033416 | 65/1556 | 0.0000952 |
| GO:0050808 | synapse organization | 2.146128 | 0.0945592 | 0.0049189 | 72/1486 | 0.0003574 |
| GO:0032279 | asymmetric synapse | 2.287187 | 0.0982668 | 0.0023511 | 58/1556 | 0.0000692 |
| GO:0050804 | modulation of chemical synaptic transmission | 2.364855 | 0.0947766 | 0.0066467 | 71/1486 | 0.0004484 |
| GO:0099177 | regulation of trans-synaptic signaling | 2.363625 | 0.0947335 | 0.0073571 | 71/1486 | 0.0004633 |
| GO:0014069 | postsynaptic density | 2.260041 | 0.0985094 | 0.0066693 | 56/1556 | 0.0001841 |
| GO:0023061 | signal release | 2.161013 | 0.0945151 | 0.0238989 | 70/1486 | 0.0011339 |
| GO:0030133 | transport vesicle | 2.225514 | 0.0968683 | 0.0250537 | 59/1556 | 0.0006707 |
| GO:1904062 | regulation of cation transmembrane transport | 2.206381 | 0.0988430 | 0.0240089 | 56/1486 | 0.0011339 |
| GO:0099513 | polymeric cytoskeletal fiber | 1.741064 | 0.0917699 | 0.0583565 | 78/1556 | 0.0013219 |
| GO:0050890 | cognition | 1.969506 | 0.0998270 | 0.0905656 | 51/1486 | 0.0033379 |
Enrichments for Module #84AD00 (MTcor=-0.93):
GSEA has 0 enriched terms
ORA has 9 enriched terms
0 terms are enriched in both methods
Plots of the results when there are more than 5 terms in common between methods:
plot_results(GSEA_GO, ORA_GO)
compare_methods(GSEA_DO, ORA_DO)
Enrichments for Module #73B000 (MTcor=0.94):
GSEA has 137 enriched terms
ORA has 0 enriched terms
0 terms are enriched in both methods
Enrichments for Module #EE8045 (MTcor=0.93):
GSEA has 128 enriched terms
ORA has 3 enriched terms
2 terms are enriched in both methods
| ID | Description | NES | pval_GSEA | pval_ORA | GeneRatio | qvalue |
|---|---|---|---|---|---|---|
| DOID:1579 | respiratory system disease | 2.273814 | 0.0106829 | 0.0467996 | 44/363 | 0.0161951 |
| DOID:0050161 | lower respiratory tract disease | 2.276961 | 0.0108113 | 0.0510984 | 41/363 | 0.0161951 |
Enrichments for Module #00B9E3 (MTcor=-0.93):
GSEA has 111 enriched terms
ORA has 1 enriched terms
1 terms are enriched in both methods
| ID | Description | NES | pval_GSEA | pval_ORA | GeneRatio | qvalue |
|---|---|---|---|---|---|---|
| DOID:1826 | epilepsy syndrome | 2.070965 | 0.0109172 | 0.0320472 | 39/687 | 0.0320472 |
Enrichments for Module #84AD00 (MTcor=-0.93):
GSEA has 103 enriched terms
ORA has 0 enriched terms
0 terms are enriched in both methods
compare_methods(GSEA_DGN, ORA_DGN)
Enrichments for Module #73B000 (MTcor=0.94):
GSEA has 0 enriched terms
ORA has 6 enriched terms
0 terms are enriched in both methods
Enrichments for Module #EE8045 (MTcor=0.93):
GSEA has 49 enriched terms
ORA has 5 enriched terms
1 terms are enriched in both methods
| ID | Description | NES | pval_GSEA | pval_ORA | GeneRatio | qvalue |
|---|---|---|---|---|---|---|
| umls:C3495559 | Juvenile arthritis | 2.37454 | 0.0496448 | 0.0196758 | 34/697 | 0.0038244 |
Enrichments for Module #00B9E3 (MTcor=-0.93):
GSEA has 6 enriched terms
ORA has 4 enriched terms
1 terms are enriched in both methods
| ID | Description | NES | pval_GSEA | pval_ORA | GeneRatio | qvalue |
|---|---|---|---|---|---|---|
| umls:C0004936 | Mental disorders | 1.688912 | 0.0431365 | 0.0441081 | 71/1413 | 0.0147027 |
Enrichments for Module #84AD00 (MTcor=-0.93):
GSEA has 0 enriched terms
ORA has 0 enriched terms
0 terms are enriched in both methods